Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer
Ning Zhao(University of Miami), Stephanie Peacock(University of Miami), Chen Hao Lo(Moffitt Cancer Center), Laine M. Heidman(University of Miami), Meghan A. Rice(University of Miami), Cale D. Fahrenholtz(University of Miami), Ann M. Greene(University of Miami), Fiorella Magani(University of Miami), Valeria A. Copello(University of Miami), Maria J. Martinez(University of Miami), Yushan Zhang(University of Florida), Yehia Daaka(University of Florida), Conor C. Lynch(Moffitt Cancer Center), Kerry L. Burnstein(University of Miami)
Cited by 76Open Access
Abstract
mRNA, were minimally affected by AVPR1A depletion. Ectopic expression of AVPR1A in androgen-dependent PC cells conferred castration resistance in vitro and in vivo. Furthermore, treatment of CRPC cells with the AVPR1A ligand, arginine vasopressin (AVP), activated ERK and CREB, known promoters of PC progression. A clinically safe and selective AVPR1A antagonist, relcovaptan, prevented CRPC emergence and decreased CRPC orthotopic and bone metastatic growth in mouse models. Based on these preclinical findings, repurposing AVPR1A antagonists is a promising therapeutic approach for CRPC.
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